不同营养状况与慢性阻塞性肺病患者预后的相关性分析

<正>慢性阻塞性肺病(chronic obstructive pulmonary diseases,COPD)在临床呼吸科发病率与病死率排名首位,使患者的生命受到严重威胁[1]。COPD患者由于消化、呼吸功衰退,营养吸收功能减弱,同时气道阻力升高,减弱了肺部顺应性,所以伴发能量不足型营养障碍的机率较高[2-3]。出现营养不良的患者往往疾病加重,影响预后,而临床COPD患者疾病严重程度与预后又同肺功能变化密切相关[4]。本文分析了不同营养状况与COPD患者预后的相关性。     

Assessment of toxicity using dehydrogenases activity and mathematical modeling

Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (T_MDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and T_MDTE are more appropriate than EC₅₀ and IC₅₀ for toxicity assessments, except for long exposure times.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

Knowledge and Usage of Emergency Contraceptives Among University Students in Ghana

Contraceptive use is an important strategy for the prevention of unwanted pregnancy and avoidance of induced abortion. Of all the contraception methods, emergency contraceptive (EC) offers the last chance to achieve this. However, few studies have documented the use of EC among young people in Ghana. This study explored knowledge and usage of EC as well as the factors associated with it among University of Cape Coast students. Data were obtained on the knowledge and usage of ECs among University of Cape Coast students in 2013. Logistic regression analysis was used to investigate the association between students’ socio-demographic characteristics and EC knowledge and use. More male students (72 %) than females (59 %) were sexually active. Fifty-seven percent of the respondents had ever heard of EC and 36 % had ever used EC. Although males were more likely to be sexually active, females were more likely to have knowledge of EC use compared to males. The study underscores the need to increase awareness regarding EC among University students in order to offer them the opportunity that EC provides if other forms of contraceptives are missed.     

Esophageal Calibration with Soft Orogasrtric Tube During Laparoscopic Nissen Fundoplication may Reduce Postoperative Transient Dysphagia

Gastroesophageal reflux is the most common benign disorder of the esophagus and laparoscopic Nissen fundoplication has become the standard surgical treatment for its treatment. In our area, where the use of bougie calibration is debatable, postoperative dysphagia is encountered often after this surgery although it is usually not permanent. The aim of this study was to investigate the effect of using a soft silicone tube 39 F in diameter for esophageal calibration during laparoscopic Nissen fundoplication on the incidence of postoperative dysphagia. We divided cases scheduled to undergo laparoscopic Nissen fundoplication between January 2009 and November 2010 into two groups, each consisting 25 patients. Esophageal calibration with a 39 F silicone orogastric tube was used for the first group while there was no operative calibration in the second group. The surgical duration was recorded; the presence and severity of the postoperative dysphagia was calculated by using a dysphagia severity scoring system during the 1-year postoperative follow-up. The dysphagia severity scores were significantly lower in group 1 than group 2 on the postoperative second day and at the end of the first week and first month. We did not find a significant difference at the end of the 6-month and first year. There was also no significant difference regarding surgery duration. The use of a soft orogastric tube 39 F in diameter for esophagus calibration during laparoscopic Nissen fundoplication has significantly decreased the incidence of postoperative transient dysphagia without affecting the duration of surgery. Although dysphagia gradually resolves in the majority of patients, a safe and easy calibration method for its prevention is worth developing, and we believe that the use of our method in larger series could be beneficial.